The allosteric protein interactions in the proton pumps of mammalian Complex IV and Complex I of the respiratory chain.

Abstract

In Complex IV (CIV) of the mammalian respiratory chain, protons are translocated from the matrix (N space) to the Mg²⁺-proton loading site by the combined conformational movements of the subunit I helix X and heme a hydroxyfarnesyl. These protons are then released into the intermembrane space (P space) through proton stereochemical transitions in the Cu_A and heme a environments.

In Complex I (CI) of mammals, the reduction of benzoquinone bound in the reaction chamber generates a negative wave that drives proton pumping from the N space to the P space via membrane domain translocator(s). During the NADH-ubiquinone oxidoreduction process, four protons are pumped. This can occur either by each of the four membrane domain translocators moving one proton each or by all four protons being pumped by a single translocator, ND5, due to its highly hydrated structure.

This paper aims to elucidate the mechanistic details and structural basis of proton pumping in these complexes, highlighting the role of allosteric protein interactions and the coupling between redox chemistry and proton translocation.

Cite:

Capitanio G, Capitanio N, Papa S (2025) The allosteric protein interactions in the proton pumps of mammalian Complex IV and Complex I of the respiratory chain. Bioenerg Commun 2025.1. https://doi.org/10.26124/bec.2025-0001